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人类冠状病毒CCoV-HuPn-2018尖端糖蛋白的结构,受体识别和抗原性
M Alejandra Tortorici1, Alexandra C Walls2, Anshu Joshi1
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
在人类中发现了一种新型犬类冠状病毒 (CCoV-HuPn-2018),突显了跨物种病毒传播的增加. 研究人员阐明了它的尖端蛋白结构,并确定了aminopeptidase N (APN) 作为其入口受体,为治疗开发铺平了道路.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 冠状病毒越来越多地被认为是具有重大公共健康影响的动物病原体.
- 从儿童呼吸道样本中出现CCoV-HuPn-2018突显了新型冠状病毒传播到人类群体的可能性.
- 了解病毒进入的分子机制对于开发有效的对策至关重要.
研究的目的:
- 描述CCoV-HuPn-2018尖端糖蛋白结构及其与宿主细胞受体的相互作用.
- 调查氨基酶N (APN) 作为CCoV-HuPn-2018的入口受体的作用.
- 探索对抗这种新兴动物性病毒的潜在交叉中和策略.
主要方法:
- 通过冷电子显微镜确定了CCoV-HuPn-2018尖端糖蛋白三元体的结构.
- 鉴定并描述了CCoV-HuPn-2018突起与犬类,猫类和猪类氨基酶N (APN) 的结合.
- 进行了基于细胞的输入测定和结构分析,用于与犬类APN复合的受体结合域.
- 评估了人类多克隆血和猪冠状病毒单克隆抗体的中和活性.
主要成果:
- CCoV-HuPn-2018尖端糖蛋白结构显示其域0识别了化物.
- 鉴定出狗,猫和猪的APN正体是CCoV-HuPn-2018的功能性入口受体.
- 确定了与犬类APN复合的受体结合B域的结构.
- 在人类APN上引入一个N739寡糖体,使得病毒容易进入,这表明宿主基因变异的作用.
- 人类和猪的抗体表现出对CCoV-HuPn-2018的交叉中和活性.
结论:
- CCoV-HuPn-2018 是第八种能够感染人类的冠状病毒,强调需要加强监测.
- 已确定的APN受体结合机制为抗病毒干预提供了目标.
- 交叉中和抗体表明阿尔法冠状病毒存在脆弱性,为广泛的疫苗和治疗开发提供了基础.
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